Showing papers in "Swiss Medical Weekly in 2013"

The impact of emotion on perception, attention, memory, and decision-making

Abstract: Reason and emotion have long been considered opposing forces. However, recent psychological and neuroscientific research has revealed that emotion and cognition are closely intertwined. Cognitive processing is needed to elicit emotional responses. At the same time, emotional responses modulate and guide cognition to enable adaptive responses to the environment. Emotion determines how we perceive our world, organise our memory, and make important decisions. In this review, we provide an overview of current theorising and research in the Affective Sciences. We describe how psychological theories of emotion conceptualise the interactions of cognitive and emotional processes. We then review recent research investigating how emotion impacts our perception, attention, memory, and decision-making. Drawing on studies with both healthy participants and clinical populations, we illustrate the mechanisms and neural substrates underlying the interactions of cognition and emotion.

Alcohol consumption in late adolescence and early adulthood - where is the problem?

Abstract: Risky single-occasion drinking (RSOD) is more common in late adolescence and early adulthood (approximately between the ages of 16 and 30) than in any other period in life. This is also the age when young people in Switzerland and many other European countries are legally allowed to buy and drink alcohol, but they usually do not yet have adult responsibilities. This paper reviews evidence from the international literature and provides examples of studies conducted in Switzerland demonstrating that (a) RSOD is by far most prevalent on Saturday evenings followed by Friday evenings, usually because young people go out and do not have any work or study responsibilities the next day; (b) RSOD results from drinking in private before going out ("predrinking") and accelerating the pace of drinking (i.e. increasing the number of drinks consumed per hour); (c) RSOD is often not accidental but purposeful,. to seek excitement, to have fun and to feel the effects of alcohol; (d) RSOD occurs predominantly outside the home, mostly in bars, pubs, discos or at special events and festivals; (e) RSOD often results in intended and unintended injuries and other acute consequences, which are leading risk factors for mortality and morbidity in this age group. Effective prevention strategies should include attempts to reduce opportunities to engage in heavy drinking as well as strategies to reduce its harmful consequences.

Vascular graft infections.

Abstract: Vascular procedures are rarely complicated by infection, but if prosthetic vascular graft infection (PVGI) occurs, morbidity and mortality are high. Several patient-related, surgery-related and postoperative risk factors are reported, but they are not well validated. PVGI is due to bacterial colonisation of the wound and the underlying prosthetic graft, generally as a result of direct contamination during the operative procedure, mainly from the patient's skin or adjacent bowel. There is no consensus on diagnostic criteria or on the best management of PVGI. On the basis of reported clinical studies and our own experience, we advocate a surgical approach combining repeated radical local debridement, with graft preservation whenever possible or partial excision of the infected graft, depending on its condition, plus simultaneous negative-pressure wound therapy (NPWT). In addition, antimicrobial therapy is recommended, but there is no consensus on which classes of agent are adequate for the treatment of PVGI and whether certain infections may be treated by means of NPWT alone. Since staphylococci and Gram-negative rods are likely to be isolated, empirical treatment might include a penicillinase-resistant beta-lactam or a glycopeptide, plus an aminoglycoside, the latter for Gram-negative coverage and synergistic treatment of Gram-positive cocci. Additionally, empirical treatment might include rifampicin since it penetrates well into biofilms.

What makes physicians go to work while sick: a comparative study of sickness presenteeism in four European countries (HOUPE).

Abstract: QUESTIONS UNDER STUDY: Sickness presenteeism is common in the health sector, especially among physicians, leading to high costs in terms of medical errors and loss in productivity. This study inves ...

Ethics and policy of medical brain drain: a review

Abstract: Health-worker migration, commonly called "medical brain drain", refers to the mass migration of trained and skilled health professionals (doctors, nurses, midwives) from low-income to high-income countries. This is currently leaving a significant number of poor countries, particularly in sub-Saharan Africa, with critical staff shortages in the healthcare sector. A broad consensus exists that, where medical brain drain exacerbates such shortages, it is unethical, and this review presents the main arguments underpinning this view. Notwithstanding the general agreement, which policies are justifiable on ethical grounds to tackle brain drain and how best to go about implementing them remains controversial. The review offers a discussion of the specific ethical issues that have to be taken into account when deciding which policy measures to prioritise and suggests a strategy of policy implementation to address medical brain drain as a matter of urgency.

Acute coronary syndrome in patients younger than 30 years--aetiologies, baseline characteristics and long-term clinical outcome.

Abstract: BACKGROUND: Coronary atherosclerosis begins early in life, but acute coronary syndromes in adults aged <30 years are exceptional. We aimed to investigate the rate of occurrence, clinical and angiographic characteristics, and longterm clinical outcome of acute coronary syndrome (ACS) in young patients who were referred to two Swiss hospitals. METHODS: From 1994 to 2010, data on all patients with ACS aged <30 years were retrospectively retrieved from our database and the patients were contacted by phone or physician’s visit. Baseline, lesion and procedural characteristics, and clinical outcome were compared between patients in whom an underlying atypical aetiology was found (non-ATS group; ATS: atherosclerosis) and patients in whom no such aetiology was detected (ATS group). The clinical endpoint was freedom from any major adverse cardiac event (MACE) during follow-up. RESULTS: A total of 27 young patients with ACS aged <30 years were admitted during the study period. They accounted for 0.05% of all coronary angiograms performed. Mean patient age was 26.8 ± 3.5 years and 22 patients (81%) were men. Current smoking (81%) and dyslipidaemia (59%) were the most frequent risk factors. Typical chest pain (n = 23; 85%) and ST-segment elevation myocardial infarction (STEMI; n = 18 [67%]) were most often found. The ATS group consisted of 17 patients (63%)

Frequency and severity of pain and symptom distress among patients with chronic kidney disease receiving dialysis.

Abstract: QUESTION UNDER STUDY: Data on pain management in haemodialysis patients with end-stage renal disease are scanty. Our study aimed to collect information on the frequency and severity of pain and symptom distress among long-term dialysis patients in southern Switzerland. METHODS: Patients with chronic kidney disease stage 5, on dialysis, treated in five nephrology units in southern Switzerland, who had given informed consent and were able to complete the survey, were interviewed to assess pain and correlated symptoms using a Visual Analogue Scale (VAS), the Brief Pain Inventory and the Edmonton Symptom Assessment System. To evaluate the impact of symptoms, the Instrumental Activities of Daily Living questionnaire was used. RESULTS: One hundred and twenty-three patients, aged 36-90 years and with a mean time on dialysis of 3.5 years, were interviewed. Pain was experienced by 81 patients during the 4 weeks before the interview: 68 had chronic pain; 66 reported pain intensity higher than 5 on the VAS; 35 identified musculoskeletal pain as the most disturbing pain. Five patients used drugs to cope with pain during the night. Asthenia and fatigue were prevalent concomitant symptoms. Asthenia, fatigue, sleep disturbances, dyspnoea, loss of appetite, nausea/vomiting and anxiety were correlated with pain. The majority of the patients reported that their pain limited their daily life activities. CONCLUSIONS: Pain severity and symptom distress in dialysis patients are important, but underestimated and undertreated. They interfere with sleep quality and daily living. Routine assessment of pain burden, pain management similar to that used in palliative care, and adequate analgesic use to treat specific dialysis-associated pain syndromes should be considered in guidelines.

Metabolomics--a novel window into inflammatory disease.

Abstract: Inflammation is an important component of normal responses to infection and injury. However, chronic activation of the immune system, due to aberrant responses to normal stimuli, can lead to the establishment of a persistent inflammatory state. Such inflammatory conditions are often debilitating, and are associated with a number of important co-morbidities including cardiovascular disease. Resting non-proliferative tissues have distinctive metabolic activities and requirements, which differ considerably from those in infiltrating immune cells, which are undergoing proliferation and differentiation. Immune responses in tissues may therefore be modulated by the relative abundance of substrates in the inflamed site. In turn immune cell activity can feed back and affect metabolic behaviour of the tissues, as most clearly demonstrated in cachexia - the loss of cellular mass driven by tumour necrosis factor-alpha (TNF-α) a key mediator of the inflammatory response. Here we discuss the potential for metabolomic analysis to clarify the interactions between inflammation and metabolic changes underlying many diseases. We suggest that an increased understanding of the interaction between inflammation and cellular metabolism, energy substrate use, tissue breakdown markers, the microbiome and drug metabolites, may provide novel insight into the regulation of inflammatory diseases.

The expression of hypoxia-inducible factor-1α and its clinical significance in lung cancer: a systematic review and meta-analysis

Abstract: Summary BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis through activation of many target genes that are especially involved in pivotal aspects of cancer biology. However, the prognostic role of HIF-1α has been controversial in primary patients with lung cancer. This metaanalysis was performed to systematically evaluate whether HIF-1α expression is associated with the clinical outcomes in lung cancer patients. METHODS: We retrieved relevant articles from Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Wan Fang Databases from inception to May 2012. Studies were selected using specific inclusion and exclusion criteria. A systematic review and meta-analysis was performed on the association between HIF-1α expression and clinical outcomes in lung cancer patients. All analyses were performed using the Revman 5.1 software. RESULTS: A total of 30 studies were identified as eligible for the systematic review and meta-analysis. The expression of HIF-1α was significantly higher than those in normal lung tissue; and III‒IV stage, lymph node metastasis, poorly differentiation, squamous cell carcinoma and small cell lung cancer (SCLC) were significantly higher than those in I‒II stage, no lymph node metastasis, well differentiation, adenocarcinomas and non small cell lung cancer (NSCLC), respectively (odds ratio (OR) = 19.00, 95% confidence interval (CI):12.12–29.78, p <0.00001; OR = 0.23, 95% CI:0.14–0.36, p <0.00001; OR = 3.72, 95% CI:2.38–5.80, p <0.00001; OR = 0.47, 95% CI:0.31–0.70, p <0.00002, OR = 0.24, 95% CI:0.07–0.77, p = 0.02; OR = 0.78, 95% CI:0.63–0.98, p = 0.03). VEGF and CA IX positive expression in HIF-1α positive tumour tissues were significantly higher than those in HIF-1α negative tumour tissues, respectively (OR = 3.23, 95% CI: 1.90–5.46, p <0.0001; OR = 3.84, 95% CI: 2.10–7.03, p <0.0001). The positive HIF-1α tumour tissues of patients had lower 5-year survival rates (OR = 0.13, 95% CI: 0.03–0.47, p = 0.002) and overall survival (relative risk (RR) = 1.68, 95% CI: 1.12–2.50, p = 0.01). CONCLUSIONS: HIF-1α is related to a differing degree of lung cancer cell, lymph node metastasis, post-operative survival time and histology (NSCLC vs. SCLC, adenocarcinomas vs. squamous cell carcinoma). HIF-1 α , which combines other proteins, such as vascular endothelial growth factor (VEGF) or CA IX, might serve as important parameters in evaluating biological behaviour and prognosis of lung cancer; it will be of benefit to clinical treatment and prognostic evaluation.

Pro- or anti-inflammatory role of apolipoprotein A-1 in high-density lipoproteins?

Abstract: Apolipoprotein A-1 (apoA-1) is the principal protein fraction of high-density lipoprotein (HDL), conferring to the latter many of its pleiotropic atheroprotective functions. After its effect on cholesterol efflux, the second most studied feature of apoA-1 is its anti-inflammatory property. In addition, it interferes with lipid peroxidation and innate immune receptors. These anti-inflammatory effects are due to various properties, in particular the ability to inhibit the transendothelial migration of immune cells by reducing integrin expression, to inhibit monocyte activation and cytokine production induced by T-cell contact, to inhibit lipid peroxidation and to interfere with innate immune receptors. Recent studies have demonstrated that during chronic systemic inflammation HDL could lose some of its atheroprotective functions and become dysfunctional or even proinflammatory. Recent evidence suggests that specific post-translational modifications of apoA-1 transform this genuine anti-inflammatory molecule into a proinflammatory one. The structural changes include chlorination, nitration and carbamylation of amino acids by myeloperoxidase, oxidation by reactive carbonyls, as well as glycation. Humoral autoimmunity to apoA-1 and HDL has been reported in populations at high cardiovascular risk and constitutes another emerging mechanism contributing to the loss of functions of apoA-1 and HDL. The fact that in recent trials cholesteryl ester transfer protein inhibitors (torcerapib and dalcetrapib) have unfortunately failed to prevent cardiovascular disease despite increasing cholesterol efflux in vitro and HDL levels in vivo, further highlights the clinical importance of understanding the mechanisms driving apoA-1 and HDL towards pro- or anti-inflammatory molecules. These findings should not affect current dyslipidaemia management guidelines.

Targeting DNA double-strand break signalling and repair: recent advances in cancer therapy.

Abstract: Genomic instability, a hallmark of almost all human cancers, drives both carcinogenesis and resistance to therapeutic interventions. Pivotal to the ability of a cell to maintain genome integrity are mechanisms that signal and repair deoxyribonucleic acid (DNA) double-strand breaks (DSBs), one of the most deleterious lesions induced by ionising radiation and various DNA-damaging chemicals. On the other hand, many current therapeutic regimens that effectively kill cancer cells are based on the induction of excessive DSBs. However, these drugs often lack selectivity for tumour cells, which results in severe side effects for the patients, thus compromising their therapeutic potential. Therefore, the development of novel tumour-specific treatment strategies is required. Unlike normal cells, however, cancer cells are often characterised by abnormalities in the DNA damage response including defects in cell cycle checkpoints and/or DNA repair, rendering them particularly sensitive to the induction of DSBs. Therefore, new anticancer agents designed to exploit these vulnerabilities are becoming promising drugs for enhancing the specificity and efficacy of future cancer therapies. Here, we summarise the latest preclinical and clinical developments in cancer therapy based on the current knowledge of DSB signalling and repair, with a special focus on the combination of small molecule inhibitors with synthetic lethality approaches.

Cost-effectiveness of dabigatran for stroke prevention in atrial fibrillation in Switzerland.

Abstract: Summary OBJECTIVES: Atrial fibrillation is a major risk factor for ischemic stroke and anticoagulation therapy is indicated to reduce risk. Dabigatran is a new oral anticoagulant that does not require INR monitoring. This study evaluated the cost-effectiveness of dabigatran versus vitamin K antagonists for stroke prevention in atrial fibrillation in Switzerland. METHODS: A Markov model simulating the course of treatment and occurrence of clinical events in two treatment arms over the lifetime of patients was adapted to the Swiss context. The adaptation included the cost of anticoagulation therapy and clinical events in Switzerland. The cost of inpatient care was estimated on data of all inpatient hospital stays in 2008. The calculation of outpatient care costs was based on peer reviewed studies, expert interviews and local tariffs. RESULTS: Patients treated with dabigatran had a higher life expectancy and experienced more quality adjusted life years (QALY) while incurring higher costs than patients treated with vitamin K antagonists. The estimated incremental cost-effectiveness ratio (ICER) was CHF 25,108.‒ per QALY with 110 mg and CHF 9,702 per QALY with 150 mg of dabigatran. A sequential dosage scheme, in which 150 mg are administered up to the age of 80 years and 110 mg thereafter, resulted in an ICER of CHF 10,215 per QALY. A sensitivity analysis confirmed that these results are robust. CONCLUSIONS: Dabigatran can be considered cost-effective in comparison with vitamin K antagonists in the Swiss context. The higher drug cost of dabigatran is compensated by savings in INR monitoring, lower cost of clinical events and QALY-gains.

Is tracheostomy still an option in amyotrophic lateral sclerosis? Reflections of a multidisciplinary work group

Abstract: Summary QUESTION UNDER STUDY: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis. Survival and quality of life of ALS patients have improved through the implementation of multidisciplinary approaches, the use of percutaneous gastrostomy and of noninvasive (NIV) or invasive ventilation. The question of whether or not to propose invasive ventilation (by tracheostomy: TPPV) to ALS patients remains a matter of debate. METHODS: The study reviews the medical literature, the practice in three Swiss and two large French ALS expert centres and reports the results of a workgroup on invasive ventilation in ALS. RESULTS: Improved management of secretions and use of different interfaces allows NIV to be used 24-hours-a-day for prolonged periods, thus avoiding TPPV in many cases. TPPV is frequently initiated in emergency situations with lack of prior informed consent. TPPV appears associated with a lesser quality of life and a higher risk of institution

The acute diabetic Charcot foot managed on the basis of magnetic resonance imaging--a review of 71 cases.

Abstract: Background Acute Charcot foot (ACF) is a skeletal breakdown associated with inflammatory swelling of a foot in patients with pain insensitivity, such as diabetic neuropathy. In ACF stage 0, skeletal pathology (e.g. osseous oedema) is visible on magnetic resonance imaging (MRI), but not on plain radiographs. Continued unprotected walking invariably causes stage 1 (complex cortical fractures). Treatment by total contact cast (TCC) is of limited benefit if X-ray-based. The benefits of MRI-based TCC treatment are unknown. Aim To assess the impact of MRI, all cases of ACF diagnosed by MRI between 2000 and 2012 were reviewed. Method Audit of medical charts of a single outpatient diabetic foot clinic. Results Seventy-one cases (59 patients) were retrieved. Diagnosis of stage 0 (n = 27 cases) and stage 1 (n = 44 cases) was established one and two months (medians) after symptom onset, respectively. Unremarkable radiographs, that were not cross-checked by MRI (n = 13 cases), misled primary care physicians to postpone referral until five months after symptom onset, when cortical fractures had already occurred in 12 cases. Midfoot (Chopart- and Lisfranc-) lesions healed better in stage 0 versus stage 1 (69% versus 7% without deformities, p = 0.0012), while forefoot (metatarsal) lesions healed well in either stage (100% versus 75% without deformities). TCC-treatment lasted four to six months. Conclusion Healing of ACF was more efficient in stage 0 than in stage 1. Expeditious MR imaging was indispensable to diagnose stage 0 in a swollen foot of a neuropathic patient, while unremarkable X-rays often led to a missed diagnosis.

Antibiotic resistance patterns among group B Streptococcus isolates: implications for antibiotic prophylaxis for early-onset neonatal sepsis

Abstract: Summary STUDY/PRINCIPLES: Antibiotic prophylaxis of Group B Streptococcus (GBS) positive women during labour reduces the risk of early-onset neonatal sepsis. Penicillin is the first choice, and clindamycin and erythromycin are second choices for penicillin-allergic women. Resistance to these antibiotics is rising. The aims of this study were to evaluate the rates of clindamycin and erythromycin resistance among GBS-positive isolates cultures from pregnant women in the University Hospital of Geneva and to evaluate the legitimacy of new Centres for Disease Control and Prevention (CDC) recommendations for our context. METHODS: We collected a vagino-rectal swab from pregnant women at 35‐37 weeks gestation. We recovered 124 GBS positive isolates. Identification was based on the characteristic of the colony on the chromogenic agar, the streptococcal agglutination test and confirmation by mass spectrometry. Antimicrobial susceptibility was determined by disk diffusion, according to CLSI guidelines 2010. RESULTS: The rate of resistance to clindamycin was 28% and to erythromycin was 30%. Only 3 of the 38 erythromycin resistant strains (7.9%) were susceptible to clindamycin, and only 3 out of the 35 clindamycin resistant GBS (8.6%) were identified as “inducible resistance”. The rate of co-resistance to clindamycin of erythromycin-resistant strains was 92%. Penicillin remained efficacious in all cases. CONCLUSION: Rates of clindamycin and erythromycin resistance are also increasing in our context. These antibiotics should not be used for GBS neonatal sepsis prevention, without adequate antimicrobial susceptibility testing. In case of penicillin allergy and lack of antibiogramm, cephalosporins or vancomycin should be used as recommended in CDC guidelines.

Perspectives using probe-based confocal laser endomicroscopy of the respiratory tract

Abstract: Questions under study/principles Although probe-based confocal laser endomicroscopy (pCLE) is on the edge of entering daily practice in gastroenterological endoscopy, findings in the field of respiratory medicine are only rarely reported, keeping pCLE during flexible bronchoscopy as a mere preclinical research tool. Since the endomicroscopic aspects of normal bronchial and alveolar tissue have recently been described, we want to take part in the development of a pCLE glossary, describing the pCLE features of pulmonary pathologies. Methods We recruited among patients referred for diagnostic bronchoscopy for pCLE imaging. Images from the central airways were obtained in every patient and alveoloscopy was performed in at least five sub-segments per patient. Results Using pCLE imaging, we were able to discriminate normal from abnormal endomicroscopical patterns in four respiratory conditions. These findings were matched with classical histopathology. Conclusion Reflecting on our own experience using pCLE imaging, we summarise the present state of knowledge, discuss five clinical cases and discuss current limitations and the future promise of this novel imaging tool.

Importance of leadership in cardiac arrest situations: from simulation to real life and back.

Abstract: The 2010 American Heart Association guidelines now recommend leadership training in Advanced Cardiac Life Support courses. In this review we provide a comprehensive summary of data derived from clinical studies that investigated the importance of leadership in cardiopulmonary resuscitation (CPR). Only a few, mostly observational, studies have been conducted under real-life conditions because of the high heterogeneity of the situations, difficulties in capturing the initial phase of CPR, and ethical issues. Well-controlled studies in the human simulator can fill existing gaps and provide important insights. High-fidelity video-assisted simulator studies from different research groups have shown that a prolonged process of teambuilding is associated with significant shortcomings in CPR, whereas effective leadership improves team performance. In addition, randomised controlled studies have provided evidence that medical students receiving leadership training subsequently showed improved CPR performance, which was sustained after a follow up of 4 months. In addition, leadership is influenced by gender and other factors such as emotional stress. Future studies are needed to investigate cultural differences and how findings from the simulator can be transferred to real-life situations.

ABC versus CAB for cardiopulmonary resuscitation: a prospective, randomized simulator-based trial

Abstract: QUESTIONS UNDER STUDY: After years of advocating ABC (Airway-Breathing-Circulation), current guidelines of cardiopulmonary resuscitation (CPR) recommend CAB (Circulation-Airway-Breathing). This trial compared ABC with CAB as initial approach to CPR from the arrival of rescuers until the completion of the first resuscitation cycle. METHODS: 108 teams, consisting of two physicians each, were randomized to receive a graphical display of either the ABC algorithm or the CAB algorithm. Subsequently teams had to treat a simulated cardiac arrest. Data analysis was performed using video recordings obtained during simulations. The primary endpoint was the time to completion of the first resuscitation cycle of 30 compressions and two ventilations. RESULTS: The time to execution of the first resuscitation measure was 32 ± 12 seconds in ABC teams and 25 ± 10 seconds in CAB teams (P = 0.002). 18/53 ABC teams (34%) and none of the 55 CAB teams (P = 0.006) applied more than the recommended two initial rescue breaths which caused a longer duration of the first cycle of 30 compressions and two ventilations in ABC teams (31 ± 13 vs.23 ± 6 sec; P = 0.001). Overall, the time to completion of the first resuscitation cycle was longer in ABC teams (63 ± 17 vs. 48 ± 10 sec; P <0.0001).CONCLUSIONS: This randomized controlled trial found CAB superior to ABC with an earlier start of CPR and a shorter time to completion of the first 30:2 resuscitation cycle. These findings endorse the change from ABC to CAB in international resuscitation guidelines.

Pubic rami fractures in the elderly--a neglected injury?

Abstract: OBJECTIVE: To evaluate the patient characteristics and natural history of pubic rami fractures in geriatric patients, with a special focus on the frequency of concomitant posterior pelvic ring lesions and the percentage of secondarily operated patients as a result of conservative treatment failure. STUDY DESIGN: Retrospective cohort study. Patients were treated in a university hospital that is equivalent to a level I Trauma centre. PATIENTS AND METHODS: We analysed 132 consecutive patients (113 women, 19 men), >65 years old, presenting with low energy-trauma pubic rami fractures at our emergency department from January 2009 to December 2011. RESULTS: Mean age of patients was 84 years (range 66-100). Women were affected six times more frequently than men. Almost 30% of patients lost their previous independence permanently owing to the injury. Ninety eight percent of previously independent patients (community dwellers) required temporary hospital care for a median duration of 39 days (interquartile range [IQR] 28-52). One-year mortality was 18.5%. A concomitant posterior pelvic ring lesion was identified by computed tomography in 54% of patients. In 4% of the patients secondary operative fracture stabilisation was performed. DISCUSSION: Pubic rami fractures are frequently associated with concomitant posterior pelvic ring injuries, making these injuries more unstable than generally assumed. Based on this fact and the long duration of hospital stay, more aggressive management of these injuries may be considered. The principle aims in this patient population are satisfying pain management, early mobilisation, conservation of independence and return to previous place of residence. Language: en

Genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors (GAPP).

Abstract: Background The pathogenesis of elevated blood pressure and other cardiovascular risk factors in the population and their progression over time is still incompletely understood, especially in young and healthy adults. Methods The genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors (GAPP) study is a population-based prospective cohort study involving a representative sample of healthy adults aged 25-41 years in the Principality of Liechtenstein. Exclusion criteria are any cardiovascular disease, diabetes, obstructive sleep apnoea syndrome, daily intake of nonsteroidal anti-inflammatory drugs and a body mass index >35 kg/m². Examinations include detailed assessment of personal, medical, lifestyle and nutritional factors, standardised assessment of weight, height and waist circumference, blood pressure measurement (clinic and 24-hour ambulatory monitoring), electrocardiography (12-lead and 24-hour Holter monitoring), bioimpedance analysis, blood, urinary and genetic sampling, spirometry and sleep pulse oximetry with nasal flow measurement. Baseline examination is still ongoing. Follow-up examinations are scheduled every 3-5 years. Results Since June 2010, 1,333 participants have been enrolled. Mean age of the participants was 36.7 ± 4.9 years and 47.5% of all participants were male. Mean body mass index was 26.1 ± 3.1 kg/m2 in men and 23.5 ± 3.9 kg/m2 in women. The prevalence of hypertension and prediabetes was 24.7% and 32.1% in men and 6% and 23% in women respectively. Mean LDL levels were 3.34 ± 0.9 mmol/l in men and 2.75 ± 0.7 mmol/l in women. Median hsCRP was 0.9 (0.5; 1.8) mg/l with no gender differences. Conclusion GAPP affords an excellent opportunity to assess genetic and phenotypic predictors of cardiovascular risk factors and their progression over time in young and healthy adults from the general population.

Hepatitis B and C in Switzerland - healthcare provider initiated testing for chronic hepatitis B and C infection

Abstract: Hepatitis B and hepatitis C are contagious liver diseases caused by the hepatitis B virus (HBV) and the hepatitis C virus (HCV), respectively. In particular, chronic infection with HBV or HCV is a major public health problem throughout Europe. The majority of persons chronically infected (65%-75%) are not aware of their infection status until symptoms of advanced liver disease appear. In addition, the peak in the number of patients suffering from advanced stages of the disease, such as cirrhosis and hepatocellular carcinoma, has not yet been reached. In order to reduce the current and future morbidity and mortality associated with chronic HBV or HCV infection, the timely detection of chronically infected persons, with follow-up and case management, is crucial. However, the current screening strategies in Europe and Switzerland have to be considered as inadequate to detect the majority of chronically infected persons. Hence, we emphasise the importance of an alternative approach: the healthcare provider initiated identification of HBV or HCV infection in defined risk groups. This entails determining whether a person is not only at risk of being chronically infected, but also at risk of becoming infected with HBV or HCV and, if necessary, testing for HBV or HCV infection.

The new licencing examination for human medicine: from concept to implementation.

Abstract: A new Swiss federal licencing examination for human medicine (FLE) was developed and released in 2011. This paper describes the process from concept design to the first results obtained on implementation of the new examination. The development process was based on the Federal Act on University Medical Professions and involved all national stakeholders in this venture. During this process questions relating to the assessment aims, the assessment formats, the assessment dimensions, the examination content and necessary trade-offs were clarified. The aims were to create a feasible, fair, valid and psychometrically sound examination in accordance with international standards, thereby indicating the expected knowledge and skills level at the end of undergraduate medical education. Finally, a centrally managed and locally administered examination comprising a written multiple-choice element and a practical “clinical skills” test in the objective structured clinical examination (OSCE) format was developed. The first two administrations of the new FLE show that the examination concept could be implemented as intended. The anticipated psychometric indices were achieved and the results support the validity of the examination. Possible changes to the format or content in the future are discussed.

Thrombocytopenia as a mortality risk factor in acute respiratory failure in H1N1 influenza.

Abstract: Summary BACKGROUND: A small proportion of patients with influenza H1N1 rapidly develop acute respiratory failure and are a problem for intensive care units (ICUs). Although certain clinical risk factors have been identified, few measurable biochemical/haematological markers able to predict poor outcome have been reported. The aims of the present report are to show which variables on and during admission are associated with increased in-hospital mortality in patients admitted to the ICU with acute respiratory failure due to H1N1 influenza. METHODS: A prospective observational study at two ICUs was carried out between August 2009 and March 2011. The study period covered two waves of pandemic influenza A H1N1 in Spain. Clinical and laboratory data on and during ICU admission were recorded for the purpose of analysis. RESULTS: Sixty patients with acute respiratory failure due to H1N1 influenza were admitted during the period described above; 63.3% (n = 38) were male and the mean age was 49.2 ± 14 years. Regarding comorbidities, 46.7% (n = 28) were smokers, 38% (n = 23) had hypertension, 30% (n = 18) had a body mass index (BMI) >30 kg/m 2 , 30% (n = 18) had chronic obstructive pulmonary disease and 26% (n = 16) had cardiac insufficiency; 16.6% (n = 10) had bacterial co-infection, 70% (n = 42) required invasive mechanical ventilation and 48.3% (n = 29) non-invasive mechanical ventilation. Mortality was 20% (n = 12). Comparing survivors with non-survivors, univariate analysis revealed significant differences in BMI, creatinine, haemoglobin, platelets, arterial pH, pCO2, and the rate of bacterial co-infection. In the multivariate analysis, only the presence of lower platelet count was statistically significant (214 ± 101 vs 113 ± 82 ×10 9 /L; p = 0.009). Patients with thrombocytopenia showed a lower in-hospital survival rate (55%vs92.5%; Log Rank = 0.008). CONCLUSIONS: Thrombocytopenia could be valuable marker of in-hospital mortality in patients with respiratory failure due to H1N1 influenza in the ICU scenario.

Meta-analysis of high-energy extracorporeal shock wave therapy in recalcitrant plantar fasciitis.

Abstract: Summary INTRODUCTION: Randomised controlled trials (RCTs) have reported conflicting results on whether extracorporeal shock wave therapy alleviates the pain of recalcitrant plantar fasciitis patients. We focused on high-energy ex- tracorporeal shock wave therapy (HESWT) and aimed to assess the effectiveness and feasibility of HESWT versus placebo in the treatment of recalcitrant plantar fasciitis. PATIENTS AND METHODS: We reviewed all RCTs com- paring HESWT and placebo from PubMed, EMBASE, Co- chrane Central Register of Controlled Trials and also the reference lists of articles. We used a fixed-effects model or a random model depending on heterogeneity and estimated the odds radio (OR) and 95% confidence interval (95% CI). Study quality was assessed using the Jadad scale. RESULTS: Five placebo-controlled and double-blinded clinical trials including 716 patients were included. Over- all, the quality of the trials was good, and a test for hetero- geneity confirmed the presence of little heterogeneity (p = 0.31, I 2 = 16%). The pooled OR from the five trials was es- timated to be 2.25 (95% CI, 1.66-3.06; p <0.00001) at 12 weeks after active treatment. CONCLUSION: The results of the meta-analysis provide strong evidence that HESWT was effective in the treatment of recalcitrant plantar fasciitis when compared with placebo. We recommend HESWT as a remedial measure after failure of traditional conservative treatment and ahead of surgical intervention.

Practical approach to early postoperative management of lung transplant recipients.

Abstract: Meticulous attention to detail during the early postoperative period after lung transplantation is crucial for the overall success of the procedure. It starts in the intensive care unit with the initiation of immunosuppression, implementation of anti-infective strategies and stabilisation of respiratory function. The subsequent days and weeks on the regular ward focus on titration of immunosuppressive drugs, vigilant fluid management, early mobilisation and initiation of physiotherapy. In parallel, the lung transplant recipients are actively taught about self-monitoring and self-management strategies to allow for a smooth transition to outpatient follow-up care. This article intends to communicate the practical aspects and principles of the patient management used at the authors' centre on a daily basis by a multi-disciplinary transplant team, having at its core both a transplant pulmonologist and a thoracic surgeon. It focuses on the first month after lung transplantation, but does not cover surgical techniques, rare complications or long-term management issues of lung transplant recipients. The target audience of this practical guide are advanced trainees of pulmonology, thoracic surgery, intensive care, anaesthesiology and other clinicians involved in the early postoperative care of lung transplant recipients either in the intensive care unit or on the peripheral ward.

Cystatin C and neutrophil gelatinase-associated lipocalin: biomarkers for acute kidney injury after congenital heart surgery.

Abstract: Questions under study To evaluate the diagnostic value of serum Cystatin C and urine neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute kidney injury in patients undergoing congenital heart surgery. Methods Serial samples of serum Cystatin C and urine NGAL were collected from 139 consecutive patients with congenital heart defects aged 3 days to 30 years after admission to the intensive care unit, 2 and 6 hours after the end of cardiopulmonary bypass. Biomarker levels were compared to perioperative data retrospectively. Acute kidney injury was defined according to the paediatric-modified RIFLE classification. Results According to the paediatric-modified RIFLE criteria 53% of patients developed evidence of acute kidney injury. Serum Cystatin C concentrations were strongly correlated with severity of acute kidney injury. Optimal sensitivity of 80% and specificity of 66% for the prediction of acute kidney injury occurred at a cut-off value of 0.995 mg/l, 2 hours after the end of cardiopulmonary bypass. The 2 hour urine NGAL concentration was significantly correlated to the duration of cardiopulmonary bypass, time of aortic cross clamping, and serum lactate concentration. Moreover a significant correlation was found between urine NGAL and both length of hospital stay and mechanical ventilation. Conclusions In patients after congenital heart surgery, urine NGAL indicates the damaging force of cardiopulmonary bypass and serum Cystatin C is a valuable predictive biomarker for resulting acute kidney injury.

Tick related diseases in Switzerland, 2008 to 2011.

Abstract: Summary QUESTION UNDER STUDY: To determine the incidence and determinants of tick related diseases in Switzerland, such as tick bites and Lyme borreliosis in primary care and tick borne encephalitis. METHODS: Analysis of the Swiss data collected by mandatory and facultative surveillance systems for the reporting period of 2008 to 2011. RESULTS: Tick related diseases in Switzerland are common. About 17,000 to 23,000 estimated cases of tick bites lead to a consultation (yearly incidence 254 per 100,000 inhabitants); about 7,000 to 12,000 estimated cases of Lyme borreliosis (yearly incidence 131 per 100,000 inhabitants) and 98 to 172 cases of tick borne encephalitis occur each year (yearly incidence 1.6 per 100,000 inhabitants). The most affected area is the north-eastern part of Switzerland. Whereas cases of tick borne encephalitis are restricted to local endemic areas, cases of Lyme borreliosis and tick bites are spread all over Switzerland. CONCLUSIONS: Tick related diseases are frequent and widespread in Switzerland. They are leading to a considerable usage of the health care system. Thus, tick bite prevention and vaccination against tick borne encephalitis are essential. However, long term follow-up cohort studies with reasonably large study populations after tick bite would be required to elucidate the risk of developing a tick borne disease.

Social and regional variations in health status and health behaviours among Swiss young adults.

Abstract: OBJECTIVE To provide nationwide data on health status and health behaviours among young adults in Switzerland, and to illustrate social and regional variations. METHODS Data came from the Swiss Federal Surveys of Adolescents, conducted in 2010/11. The sample consisted of 32,424 young men and 1,467 young women. We used logistic regression models to examine patterns of social inequality for three measures of health status and three measures of health behaviour. RESULTS Among men, lower self-rated health, overweight and lower physical fitness levels were associated with lower educational and fewer financial resources. Patterns were similar among young women. Unfavourable self-rated health (odds ratio [OR]: men 0.83, women 0.75) and overweight (OR: men 0.84, women 0.85; p >0.05) were less common in the French- than in the German-language region. Low physical fitness was more common in the French- than in the German-language region. In both sexes, daily smoking was associated with fewer educational resources, and physical inactivity was associated with lower educational and fewer financial resources. Males from the Italian-language region were three times more likely to be physically inactive than their German-speaking counterparts (OR 2.95). Risk drinking was more widespread among males in the French- than in the German-speaking language region (OR 1.47). CONCLUSIONS Striking social and moderate regional differences exist in health status and health behaviours among young Swiss males and females. The current findings offer new empirical evidence on social determinants of health in Switzerland and suggest education, material resources and regional conditions to be addressed in public health practice and in more focused future research.

Potentials and pitfalls of clinical peptidomics and metabolomics

Abstract: Clinical peptidomics and metabolomics are two emerging "-omics" technologies with the potential not only to detect disease-specific markers, but also to give insight into the disease dependency of degradation processes and metabolic pathway alterations. However, despite their rapid evolution and major investments, a clinical breakthrough, such as the approval of a major cancer biomarker, is still out of sight. What are the reasons for this failure? In this review we focus on three important factors: sensitivity, specificity and the avoidance of bias. The way to clinical implementation of peptidomics and metabolomics is still hampered by many of the problems that had to be solved for genomics and proteomics in the past, as well as new ones that require the creation of new analytic, computational and interpretative techniques. The greatest challenge, however, will be the integration of information from different "-omics" subdisciplines into straightforward answers to clinical questions, for example, in the form of new, superior "meta-markers".

Complementary and alternative medicine in paediatrics: a systematic overview/synthesis of Cochrane Collaboration reviews.

Abstract: Background A high prevalence of complementary and alternative medicine (CAM) use has been documented in children with chronic illnesses. Conversely, evidence-based medicine is considered an important contributor in providing the best quality of care. Methods We performed a systematic overview/synthesis of all Cochrane reviews published between 1995 and 2012 in paediatrics that assessed the efficacy, and clinical implications and limitations of CAM use in children. Main outcome variables were: percentage of reviews that concluded that a certain intervention provides a benefit, percentage of reviews that concluded that a certain intervention should not be performed, and percentage of studies that concluded that the current level of evidence is inconclusive. Results A total of 135 reviews were included - most from the United Kingdom (29/135), Australia (24/135) and China (24/135). Only 5/135 (3.7%) reviews gave a recommendation in favour of a certain intervention; 26/135 (19.4%) issued a conditional positive recommendation, and 9/135 (6.6%) reviews concluded that certain interventions should not be performed. Ninety-five reviews (70.3%) were inconclusive. The proportion of inconclusive reviews increased during three, a priori-defined, time intervals (1995-2000: 15/27 [55.6%]; 2001-2006: 33/44 [75%]; and 2007-2012: 47/64 [73.4%]). The three most common criticisms of the quality of the studies included were: more research needed (82/135), low methodological quality (57/135) and small number of study participants (48/135). Conclusions Given the disproportionate number of inconclusive reviews, there is an ongoing need for high quality research to assess the potential role of CAM in children. Unless the study of CAM is performed to the same science-based standards as conventional therapies, CAM therapies risk being perpetually marginalised by mainstream medicine.